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10.1126/science.1163595
82,795,656
Cells sense the environment's mechanical stiffness to control their own shape, migration, and fate. To better understand stiffness sensing, we constructed a stochastic model of the “motor-clutch” force transmission system, where molecular clutches link F-actin to the substrate and mechanically resist myosin-driven F-ac...
10.1038/nature10316
This study proposes and validates a model describing rigidity sensitive FA dynamics in terms of force-activated protein dissociation.
10.1083/jcb.200810002
83,123,720
Binding of integrins to ligands provides anchorage and signals for the cell, making them prime candidates for mechanosensing molecules. How force regulates integrin–ligand dissociation is unclear. We used atomic force microscopy to measure the force-dependent lifetimes of single bonds between a fibronectin fragment and...
10.1038/nature10316
This study shows that the linkage between α 5 β 1 integrin and fibronectin acts like a catch bond at the single molecule level.
10.1126/science.1168441
123,117,067
The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that α 5 β 1 integrin swi...
10.1038/nature10316
This study shows that force and increased extracellular rigidity switch α 5 β 1 integrin between a relaxed and a tensioned state that is required for mechanically induced focal adhesion kinase signalling.
10.1175/jcli-d-12-00554.1
104,332,568
Abstract The carbon cycle is a crucial Earth system component affecting climate and atmospheric composition. The response of natural carbon uptake to CO2 and climate change will determine anthropogenic emissions compatible with a target CO2 pathway. For phase 5 of the Coupled Model Intercomparison Project (CMIP5), four...
10.1038/nclimate3071
This study laid out the idea of 'allowable emissions', highlighting the importance of terrestrial carbon cycle uncertainty in projecting allowable greenhouse gas emissions that are compatible with specified climate targets.
10.1111/gcb.12718
124,641,334
Abstract Soil carbon cycling processes potentially play a large role in biotic feedbacks to climate change, but little agreement exists at present on what the core of numerical soil C cycling models should look like. In contrast, most canopy models of photosynthesis and leaf gas exchange share a common ‘Farquhaur‐model...
10.1038/nclimate3071
This opinion piece proposed a modular model structure to represent the complexity of processes influencing soil C turnover, bringing representations of soil C turnover in line with those of photosynthesis in ecosystem and global models.
10.1111/gcb.12982
107,143,003
Abstract Labile, ‘high‐quality’, plant litters are hypothesized to promote soil organic matter ( SOM ) stabilization in mineral soil fractions that are physicochemically protected from rapid mineralization. However, the effect of litter quality on SOM stabilization is inconsistent. High‐quality litters, characterized b...
10.1038/nclimate3071
This opinion laid out a new conceptual model that integrates advances in understanding of how microbial physiology controls soil C cycling, with established physico-chemical principles that dictate whether physiological responses influence soil C stocks.
10.1046/j.1365-2486.2003.00677.x
82,920,291
Abstract Accounting for CO 2 fluxes by determining changes in stocks of soil carbon (C) as a result of land use change is an option for complying nations under the Kyoto Protocol. The 1996 IPCC guidelines for C accounting recommend that soil C stocks to a depth of 30 cm be used in such accounting. However, the soil bul...
10.1038/nclimate3071
This study showed how conventional soil sampling procedures might fail to measure real changes in soil C stocks with time, and the authors proposed that a mass-dependent method be broadly adopted to address these issues.
10.1002/anie.200703883
38,419,335
Abstract The chemistry of heterocyclic carbenes has experienced a rapid development over the last years. In addition to the imidazolin‐2‐ylidenes, a large number of cyclic diaminocarbenes with different ring sizes have been described. Aside from diaminocarbenes, P‐heterocyclic carbenes, and derivatives with only one, o...
10.1038/nature13384
This is an excellent comprehensive review summarising the synthesis and coordination chemistry of a range of NHCs.
10.1002/anie.201102717
41,752,790
Abstract Boranes are widely used Lewis acids and N‐heterocyclic carbenes (NHCs) are popular Lewis bases, so it is remarkable how little was known about their derived complexes until recently. NHC‐boranes are typically readily accessible and many are so stable that they can be treated like organic compounds rather than ...
10.1038/nature13384
This review provides an excellent summary of the synthesis and reactivity of NHC–borane adducts.
10.1126/science.1241214
83,536,166
The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of t...
10.1038/nature18846
This study showed that a microbiota from a lean individual could invade the microbiota of an obese individual and provide protection from weight gain, but that the invasion and protection was dependent on diet.
10.1073/pnas.1005963107
83,539,810
Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural Afr...
10.1038/nature18846
The first of several studies to show that the gut microbiota of a traditional rural population is more diverse than and contains distinct taxa in comparison to the microbiotas of Western populations.
10.2337/db06-1491
62,303,607
Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotox...
10.1038/nature18846
The first study to demonstrate that the presence of endotoxin is sufficient to alter glucose metabolism in mice.
10.1039/c5gc01694k
83,038,587
Completely bio-based high molecular weight aliphatic poly(limonene carbonate) with excellent transparency, superior hardness compared to BPA-PC and a high T g of 130 °C.
10.1038/nature21001
This paper demonstrates the production and scale-up of fully bio-based polylimonene carbonate, prepared through the copolymerization of carbon dioxide with epoxide, and evaluates its properties.
10.1039/c4gc00513a
19,178,884
Life cycle assessment is used to determine impact reductions for greenhouse gas emission and fossil resource depletion for production of polyethercarbonate polyols using CO 2 from flue gases as feedstock.
10.1038/nature21001
This paper presents a life-cycle assessment that compares the production of polyols for polyurethane manufacture from petrochemical sources or through partial substitution with carbon dioxide.
10.1002/anie.201410211
17,638,018
Abstract We report the cocrystallization of the regio‐ and stereoregular chiral copolymer poly(limonene carbonate). To the best of our knowledge, this marks the first example of an amorphous, enantiomerically pure polymer that becomes crystalline upon stereocomplexation with its complementary enantiomer. By analyzing X...
10.1038/nature21001
This paper demonstrates the production of polylimonene carbonate stereocomplexes through efficient catalysis.
10.1002/aenm.201501010
83,368,885
Ni‐rich layered oxides and Li‐rich layered oxides are topics of much research interest as cathodes for Li‐ion batteries due to their low cost and higher discharge capacities compared to those of LiCoO 2 and LiMn 2 O 4 . However, Ni‐rich layered oxides have several pitfalls, including difficulty in synthesizing a well‐o...
10.1038/natrevmats.2016.13
This article addresses key challenges in the synthesis and battery operation of high-capacity layered oxide cathodes and outlines future research directions.
10.1039/c4cs00015c
41,768,720
In this review, the fundamentals, challenges and latest exciting advances related to zinc–air research are highlighted.
10.1038/natrevmats.2016.13
Detailed effects of cell components in primary and secondary Zn–air batteries on the electrochemical performance are discussed in this article, focusing on the cells' operation principles, technical issues and potential solutions.
10.1126/science.1108451
29,110,098
Kai proteins globally regulate circadian gene expression of cyanobacteria. The KaiC phosphorylation cycle, which persists even without transcription or translation, is assumed to be a basic timing process of the circadian clock. We have reconstituted the self-sustainable oscillation of KaiC phosphorylation in vitro by ...
10.1038/nature11704
This paper reports the reconstitution of the first circadian reaction in vitro in the presence of just protein and ATP.
10.1126/science.1060698
125,142,365
Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle. Although built to fluctuate at or near a 24-hour cycle, the clock can be entrained by light, activity, or food. Here we show that the DNA-binding activity of the Clock:BMAL1 and NPAS2:...
10.1038/nature11704
This paper initiated the hypothesis that circadian cycles arise from metabolic cycles.
10.1101/gad.183500
41,471,951
In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feedi...
10.1038/nature11704
The work in this report followed pioneering studies, by the same group, demonstrating cell-autonomous oscillation of the circadian clock in fibroblasts, and provided the first evidence for peripheral molecular clock entrainment to feeding.
10.1126/science.1108750
20,760,996
The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptin...
10.1038/nature11704
This article reports work that opened genetic approaches to probe links between clocks and metabolism.
10.1126/science.1172156
107,220,894
Coupling Clocks and Metabolism Circadian clocks in mammals coordinate behavior and physiology with daily light-dark cycles by driving rhythmic transcription of thousands of genes. The master clock in the brain is set by light, but clocks in peripheral tissues, such as the liver, are set by daily feeding. Such coupling ...
10.1038/nature11704
This study introduces a molecular mechanism for feedback regulation of the internal clock through metabolic flux.
10.1126/science.1198125
62,496,189
Circadian control of liver metabolism is mediated by cycles of recruitment of the histone deacetylase HDAC3.
10.1038/nature11704
This paper integrates genomic approaches to illustrate the epigenetic mechanisms that link circadian oscillation with metabolism.
10.1126/science.1170803
125,142,649
Circadian Oscillations The 24-hour day-night cycle plays an important role in mammalian physiology and behavior and, as most travelers are well aware, there is an intimate link between our in-built circadian clocks and metabolic rhythms. This link is in part forged by the protein deacetylase SIRT1, which regulates the ...
10.1038/nature11704
References 81 and 82 make up work that defines a feedback loop linking NAD + biosynthesis to circadian oscillation.
10.1126/science.276.5315.1109
83,278,162
Single-molecule atomic force microscopy (AFM) was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle. Individual titin molecules were repeatedly stretched, and the applied force was recorded as a function of the elongation. At large extensions, the restoring force ex...
10.1038/natrevmats.2017.8
This paper characterizes the mechanically induced unfolding and reversible refolding of single protein domains using AFM-based SMFS.
10.1126/science.288.5463.143
62,577,968
Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum . Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces betwee...
10.1038/natrevmats.2017.8
This paper describes the mechanically induced stepwise unfolding of membrane proteins using AFM-based SMFS.
10.1126/science.288.5464.316
61,649,262
We report the specific transduction, via surface stress changes, of DNA hybridization and receptor-ligand binding into a direct nanomechanical response of microfabricated cantilevers. Cantilevers in an array were functionalized with a selection of biomolecules. The differential deflection of the cantilevers was found t...
10.1038/natrevmats.2017.8
This study introduces the use of microcantilevers to sense biomolecular binding.
10.1126/science.2464851
82,283,879
A scanning ion-conductance microscope (SICM) has been developed that can image the topography of nonconducting surfaces that are covered with electrolytes. The probe of the SICM is an electrolyte-filled micropipette. The flow of ions through the opening of the pipette is blocked at short distances between the probe and...
10.1038/natrevmats.2017.8
This classic study describes the invention of scanning ion conductance microscopy.
10.1126/science.1195628
83,508,861
We report the creation of a nanoscale electrochemical device inside a transmission electron microscope—consisting of a single tin dioxide (SnO 2 ) nanowire anode, an ionic liquid electrolyte, and a bulk lithium cobalt dioxide (LiCoO 2 ) cathode—and the in situ observation of the lithiation of the SnO 2 nanowire during ...
10.1038/nenergy.2017.11
This paper reports the first attempt to create a nanoscale electrochemical device inside a transmission electron microscope and observes in-situ the lithiation of the SnO 2 nanowire during electrochemical charging.
10.1126/science.1241882
107,153,484
Battery Breakdown Although a range of materials can be used for chemically storing electrical charge, many cannot be made into batteries that retain their capacity over many cycles. Failure may be because of secondary reactions, poisoning through the formation of surface coatings, or volumetric changes leading to fract...
10.1038/nenergy.2017.11
Using material tin( II ) oxide as a model material this paper highlights tomography as a tool to guide the development of durable materials and strain-tolerant electrodes.
10.1063/1.1499754
20,640,173
We analyze surface codes, the topological quantum error-correcting codes introduced by Kitaev. In these codes, qubits are arranged in a two-dimensional array on a surface of nontrivial topology, and encoded quantum operations are associated with nontrivial homology cycles of the surface. We formulate protocols for erro...
10.1038/nature23460
Seminal paper on using the surface code as a quantum memory
10.1098/rspb.2007.1391
15,819,198
The complex spatio-temporal patterns of development and anatomy of nervous systems play a key role in our understanding of arthropod evolution. However, the degree of resolution of neural processes is not always detailed enough to claim homology between arthropod groups. One example is neural precursors and their proge...
10.1038/nature07890
This paper presents data typical of the high-quality morphological techniques now being used to address arthropod phylogeny.
10.1098/rspb.2007.0429
119,763,912
A new arthropod with three-dimensionally preserved soft parts, Tanazios dokeron , is described from the Wenlock Series (Silurian) of Herefordshire, England, UK. Serial grinding, digital photographic and computer rendering techniques yielded ‘virtual fossils’ in the round for study. The body tagmata of T. dokeron compri...
10.1038/nature07890
This paper provides valuable new data on a crustacean-like taxon considerably younger than the Cambrian faunas.
10.1146/annurev.micro.091208.073248
80,597,967
Our view of bacteria, from the earliest observations through the heyday of antibiotic discovery, has shifted dramatically. We recognize communities of bacteria as integral and functionally important components of diverse habitats, ranging from soil collectives to the human microbiome. To function as productive communit...
10.1038/nchembio.739
This review discusses the influence that a bacterium has within a community through participating in metabolic exchange.
10.1146/annurev.micro.52.1.81
61,242,299
▪ Abstract It has been a decade since multicellularity was proposed as a general bacterial trait. Intercellular communication and multicellular coordination are now known to be widespread among prokaryotes and to affect multiple phenotypes. Many different classes of signaling molecules have been identified in both Gram...
10.1038/nchembio.739
This review is one of the first to discuss bacterial populations as multidimensional organisms.
10.1126/science.2781297
41,320,852
Embryos of the shrimp Palaemon macrodactylus are remarkably resistant to infection by the fungus Lagenidium callinectes , a recognized pathogen of many crustaceans. An Alteromonas sp. bacterial strain consistently isolated from the surface of the embryos, produces 2,3-indolinedione (isatin), a compound that inhibits th...
10.1038/nchembio.739
This provides an excellent example of the roles of metabolic exchange factors produced by symbiotic bacteria in host survival.
10.1073/pnas.1008441108
59,267,529
Leaf-cutting ants cultivate the fungus Leucoagaricus gongylophorus , which serves as a major food source. This symbiosis is threatened by microbial pathogens that can severely infect L. gongylophorus . Microbial symbionts of leaf-cutting ants, mainly Pseudonocardia and Streptomyces , support the ants in defending their...
10.1038/nchembio.739
This work used new methodologies to characterize the metabolic exchange between microbial communities within the nests of leaf-cutting ants.
10.1073/pnas.1101134108
38,252,195
Microbes in nature frequently function as members of complex multitaxon communities, but the structural organization of these communities at the micrometer level is poorly understood because of limitations in labeling and imaging technology. We report here a combinatorial labeling strategy coupled with spectral image a...
10.1038/nchembio.739
This paper represents an example of the use of labeling and imaging approaches to visualize and differentiate phylotypes of microbial communities.
10.1073/pnas.1008368107
125,256,429
During bacterial cannibalism, a differentiated subpopulation harvests nutrients from their genetically identical siblings to allow continued growth in nutrient-limited conditions. Hypothesis-driven imaging mass spectrometry (IMS) was used to identify metabolites active in a Bacillus subtilis cannibalism system in which...
10.1038/nchembio.739
This is the first work to apply IMS to discover specific factors that are active in microbial intraspecies interactions.
10.1146/annurev.genet.42.110807.091449
84,534,830
Bacteria have developed remarkable systems that sense neighboring target cells upon contact and initiate a series of events that enhance their survival and growth at the expense of the target cells. Four main classes of bacterial cell surface structures have been identified that interact with prokaryotic or eukaryotic ...
10.1038/nchembio.739
This comprehensive review discusses the contact-dependent systems that microbes use to interact with each other and their environment.
10.1126/science.1205970
65,526,336
Compounds recognized as having antibiotic functions may have other possible roles in microbial interactions.
10.1038/nchembio.739
This article discusses the possibility that there may be several roles for antibiotics in the native environment of microbes.
10.1073/pnas.0810634105
38,734,720
Although the role of liganded nuclear receptors in mediating coactivator/corepressor exchange is well-established, little is known about the potential regulation of chromosomal organization in the 3-dimensional space of the nucleus in achieving integrated transcriptional responses to diverse signaling events. Here, we ...
10.1038/nature08453
This report demonstrates that chromatin crosstalk involves directed rapid movement of interacting loci and that this process is frequently accompanied by reorganization of the chromosome territories.
10.1111/j.1461-0248.2010.01439.x
83,124,228
Ecology Letters (2010) 13: 464–472 Abstract Predicting regime shifts – drastic changes in dynamic behaviour – is a key challenge in ecology and other fields. Here we show that the class of ecological systems that will exhibit leading indicators of regime shifts is limited, and that there is a set of ecological models a...
10.1038/nature11018
This paper points out that regime shifts in complex systems need not result from saddle-node bifurcations and thus may not show the typical early warning signals.
10.1126/science.1212267
62,288,570
Deposition of reactive nitrogen from human activities occurred in the preindustrial era.
10.1038/nature11018
This paper documents how human impacts are reaching into remote ecosystems.
10.1073/pnas.0806823106
83,409,680
Darwin's classic image of an “entangled bank” of interdependencies among species has long suggested that it is difficult to predict how the loss of one species affects the abundance of others. We show that for dynamical models of realistically structured ecological networks in which pair-wise consumer-resource interact...
10.1038/nature11018
This computational exploration of complex network structure and dynamics successfully predicts the quantitative effect of a species loss on other species within its community and therefore demonstrates the potential of ecological network theory to predict state changes following species loss.
10.1111/gcb.12752
20,697,981
Abstract Soil biodiversity plays a key role in regulating the processes that underpin the delivery of ecosystem goods and services in terrestrial ecosystems. Agricultural intensification is known to change the diversity of individual groups of soil biota, but less is known about how intensification affects biodiversity...
10.1038/nature15744
This study, encompassing four agricultural regions across Europe, showed that increasing land-use intensity reduced soil foodweb diversity, functional diversity and taxonomic diversity.
10.1073/pnas.1205624109
60,834,061
Rapidly declining biodiversity may be a contributing factor to another global megatrend—the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the “biodiversity hypothesis,” reduced contact of people with natural environmental features and ...
10.1038/nature15744
This study provides evidence that people living near environmentally diverse areas had less propensity for allergies because of a greater diversity of commensal bacteria on their skin, most of which are also found in soil and vegetation.
10.1073/pnas.1109326109
123,208,247
Natural ecosystems show variable resistance to invasion by alien species, and this resistance can relate to the species diversity in the system. In soil, microorganisms are key components that determine life support functions, but the functional redundancy in the microbiota of most soils has long been thought to overwh...
10.1038/nature15744
Experimental results showed that in soils with greater microbial diversity invading bacteria have a lower survival rate.
10.1126/science.aaa5594
27,007,686
Schadt and Rosling (Technical Comment, 26 June 2015, p. 1438) argue that primer-template mismatches neglected the fungal class Archaeorhizomycetes in a global soil survey. Amplicon-based metabarcoding of nine barcode-primer pair combinations and polymerase chain reaction (PCR)–free shotgun metagenomics revealed that ba...
10.1038/nature15744
This analysis indicates that the distribution and species richness of fungi is mostly determined by climate and not related to plant diversity on a global scale, except for root-related ectomycorrizal fungi; biogeographical comparisons of continents indicate efficient dispersal mechanisms for fungi compared to larger o...
10.1017/cbo9780511814679
38,206,469
People today must make decisions about many health, safety, and environmental risks. Nuclear power, HIV/AIDS, radon, vaccines, climate change, and emerging infectious diseases are just some issues that may face them in the news media, ballot box, or doctor's office. In order to make sound choices they need to get good ...
10.1038/nclimate1080
This book develops a methodological approach to integrating risk analysis and risk communication, focusing analysis on decision makers' needs and communication on critical gaps.
10.1002/wcc.11
83,125,637
Abstract Since anthropogenic climate change first emerged on the public agenda in the mid‐to‐late 1980s, public communication of climate change and—more recently—the question of how to communicate it most effectively have witnessed a steep rise. This paper synthesizes what is known, presumed, and still unknown about ho...
10.1038/nclimate1080
An informative review of basic research findings on risk communication as applied to climate change
10.1038/ncomms11152
17,582,771
Abstract Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and dev...
10.1038/nchembio.2429
This study lays the groundwork for repurposing yeast organelles to compartmentalize metabolic pathways. Focusing on the peroxisome, the authors developed an assay for cargo import, measured membrane permeability, and identified an amino acid linker that enhances targeting of heterologous enzymes to the organelle
10.1126/science.1130256
122,987,270
Yeast is a widely used recombinant protein expression system. We expanded its utility by engineering the yeast Pichia pastoris to secrete human glycoproteins with fully complex terminally sialylated N-glycans. After the knockout of four genes to eliminate yeast-specific glycosylation, we introduced 14 heterologous gene...
10.1038/nchembio.2429
A report summarizing the successful culmination of efforts to produce humanized, terminally sialylated complex glycoproteins with therapeutic utility in yeast. After knocking out genes involved in yeast glycosylation, authors introduced heterologous mannosidases, glycosyltransferases, nucleotide sugar transporters, and...
10.2337/db09-1918
81,731,186
OBJECTIVE Depletion of body fat stores during uncontrolled, insulin-deficient diabetes (uDM) results in markedly reduced plasma leptin levels. This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM. RESEARCH ...
10.1038/nature11705
In this article, the authors show that brain leptin injection — in the absence of endogenous or exogenous insulin — suffices to normalize blood glucose.
10.1038/ncomms12570
124,484,041
Abstract Plants resist infection and herbivory with innate immune responses that are often associated with reduced growth. Despite the importance of growth-defense tradeoffs in shaping plant productivity in natural and agricultural ecosystems, the molecular mechanisms that link growth and immunity are poorly understood...
10.1038/nature22010
This study describes genetic changes in plants that result in the parallel activation of transcriptional programs for jasmonic-acid-dependent defence and light-signalling-dependent growth, revealing that there is no growth–defence trade-off; such plants can therefore be used as tools with which to study the fitness con...
10.1111/1365-2435.12690
26,793,213
Summary While an appreciation of plant–soil feedbacks ( PSF ) continues to expand for community and ecosystem ecology, the eco‐evolutionary mechanisms and consequences of such feedbacks remain largely unknown or untested. Determining the cause and effect of plant phenotypes is central for understanding these eco‐evolut...
10.1038/nature22010
Complex plant–soil feedback interactions are now recognized as being able to drive the evolution of plant traits; this review discusses how environmental gradients may drive the evolution of plant traits and how such evolution feeds back to the entire ecosystem.
10.1111/j.1466-8238.2012.00771.x
42,622,616
ABSTRACT Aim Although many studies support the prevailing paradigm of nitrogen (N)‐driven biodiversity loss, some have argued that phosphorus (P) may be the main culprit. This questions the generality of the global threat through N enrichment. The major objective here was to quantify the relative importance of soil N a...
10.1038/nature22010
This study provides a new framework for promoting the understanding of disease dynamics and how research on species that attack plants can be linked to community ecology; when linked to a plant trait-based methods, such an approach can help to bridge the gap between ecology and molecular biology.
10.1073/pnas.91.12.5682
79,425,198
During the formation of the mitotic spindle, dynamic microtubules search for chromosomes in the surrounding cytosol. The average time required to reach such "targets" is calculated within a simple model of dynamic instability. The values of the dynamic parameters that minimize this search time are also obtained. The re...
10.1038/nature08908
This paper showed that microtubule dynamics have a central role in spatial organization within cells.
10.1073/pnas.95.11.6181
83,491,863
The Arp2/3 complex is a stable assembly of seven protein subunits including two actin-related proteins (Arp2 and Arp3) and five novel proteins. Previous work showed that this complex binds to the sides of actin filaments and is concentrated at the leading edges of motile cells. Here, we show that Arp2/3 complex purifie...
10.1038/nature08908
This paper presented the dendritic nucleation model for the assembly of branched actin networks.
10.1073/pnas.68.4.820
20,848,282
Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, ...
10.1038/nature10275
The original statistical analysis of hereditary retinoblastoma that led to the two-hit hypothesis.
10.1146/annurev-psych-010213-115202
104,241,367
Adolescence is a period of formative biological and social transition. Social cognitive processes involved in navigating increasingly complex and intimate relationships continue to develop throughout adolescence. Here, we describe the functional and structural changes occurring in the brain during this period of life a...
10.1038/nature25770
This study describes how brain regions involved in social processing and behaviour undergo both structural changes and functional reorganization during the second decade of life, possibly reflecting a sensitive period for adapting to one’s social environment.
10.1177/1745691617722620
82,496,769
We provide a developmental perspective on two related issues: (a) why traditional preventative school-based interventions work reasonably well for children but less so for middle adolescents and (b) why some alternative approaches to interventions show promise for middle adolescents. We propose the hypothesis that trad...
10.1038/nature25770
This study provides a developmental perspective as to why traditional preventative school-based interventions work less well for adolescents, and reviews examples of promising approaches that take into account adolescents’ enhanced desire to feel respected and be accorded status.
10.1126/science.1164097
109,445,740
Chromatin Modifier Modulates Gene Expression Modification of chromatin structure is usually thought of as a global, relatively nonspecific way of modulating gene expression. However, Wellen et al. (p. 1076 ; see the Perspective by Rathmell and Newgard ) demonstrate that such regulation helps link growth factor–stimulat...
10.1038/nature12752
References 46 to 48 show that acetyl-CoA increases histone acetylation in yeast and mammalian cells when its abundance is enriched in the nucleocytosolic compartment of a cell.
10.1126/science.1226603
103,612,753
SAM, Histones, and Stem Cells Mouse embryonic stem cells require threonine for growth and express large amounts of the enzyme that catalyzes the first step in threonine metabolism. To find out what is so important about threonine in these cells, Shyh-Change et al. (p. 222 , published online 1 November; see the Perspect...
10.1038/nature12752
References 69 and 70 describe the dependence of pluripotency on the generation of S -adenosylmethionine by threonine catabolism in embryonic stem cells.
10.1126/science.1227166
104,015,382
Stress Protector During prolonged fasting, the oxidation of fatty acids leads to increased accumulation of d -β-hydroxybutyrate (βOHB) in the bloodstream. Such increased concentrations of βOHB inhibit class I histone deacetylases. Histone acetylation in turn influences transcriptional activity at various genes. Shimazu...
10.1038/nature12752
This study identifies the ketone body β-hydroxybutyrate as an endogenous inhibitor of HDACs and protective agent against oxidative damage.
10.1073/pnas.0500398102
41,533,843
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but ...
10.1038/nature12752
This study in humans shows that epigenetic marks increasingly differ during adult life of monozygotic twins.
10.1073/pnas.1003428107
38,443,445
Otto Warburg's theory on the origins of cancer postulates that tumor cells have defects in mitochondrial oxidative phosphorylation and therefore rely on high levels of aerobic glycolysis as the major source of ATP to fuel cellular proliferation (the Warburg effect). This is in contrast to normal cells, which primarily ...
10.1038/nchembio.1712
This report provides genetic and pharmacologic evidence that mitochondrial metabolism and ROS are required for tumor growth.
10.1101/gad.2016311
41,685,334
Autophagy is a catabolic pathway used by cells to support metabolism in response to starvation and to clear damaged proteins and organelles in response to stress. We report here that expression of a H-ras V12 or K-ras V12 oncogene up-regulates basal autophagy, which is required for tumor cell survival in starvation and...
10.1038/nchembio.1712
This report provides evidence that autophagy sustains mitochondrial metabolism that is essential for tumor growth.
10.1146/annurev.pharmtox.47.120505.105110
41,486,191
Mitochondrial oxidative damage contributes to a range of degenerative diseases. Consequently, the selective inhibition of mitochondrial oxidative damage is a promising therapeutic strategy. One way to do this is to invent antioxidants that are selectively accumulated into mitochondria within patients. Such mitochondria...
10.1038/nchembio.1712
An excellent review that details mechanisms by which small molecules preferentially can be delivered into mitochondrial matrix.
10.1126/science.1132898
20,651,444
We demonstrated nanoscale solid-state thermal rectification. High-thermal-conductivity carbon and boron nitride nanotubes were mass-loaded externally and inhomogeneously with heavy molecules. The resulting nanoscale system yields asymmetric axial thermal conductance with greater heat flow in the direction of decreasing...
10.1038/nature12608
This paper describes an experimental solid-state thermal diode formed by a non-uniform mass distribution in nanotubes.
10.1126/science.1245296
18,958,028
From Yeast to Therapeutic? Yeast has shown some promise as a model system to generate lead compounds that could have therapeutic potential for the cellular problems associated with neurodegenerative diseases. Along these lines, Tardiff et al. (p. 979 , published online 24 October) and Chung et al. (p. 983 , published o...
10.1038/nature20414
Cortical neurons generated from people with a mutation in α-synuclein exhibit cellular features that could be predicted from the results of an unbiased screen of a yeast α-synuclein toxicity model and that could be reversed using a small-molecule 'hit' from the screen.
10.1073/pnas.1520335113
104,438,313
Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. M...
10.1038/nature20414
Long-term cultures of human midbrain dopamine neurons from people with PD or Gaucher's disease exhibit defects in the trafficking of important lysosomal enzymes, which could be rescued by boosting the transport of vesicles.
10.1126/science.1227157
20,881,057
Synthetic Parkinson's Parkinson's disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)–containing intraneuronal inclusions—Lewy bodies (LBs) and Lewy neurites (LNs)—in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other ...
10.1038/nature20414
A single, intrastriatal injection of α-synuclein fibrils in wild-type mice initiates the templating and propagation of pathological aggregates, the loss of dopaminergic neurons and motor deficits, providing a direct mechanistic link between the spread of α-synuclein and the pathogenesis of PD.
10.1126/science.1195227
20,662,519
α-Synuclein and Aging Transgenic α-synuclein can reverse the otherwise lethal neurodegeneration of cysteine string protein-α knockout mice via changes in SNARE proteins, which mediate synaptic vesicle release. Using experiments with purified recombinant proteins, triple αβγ-synuclein knockout mice, and studies of mouse...
10.1038/nature20414
α-Synuclein is shown to function as a chaperone that facilitates the maintenance of SNARE complexes at the synapse, and Snca Sncb Sncg triple-knockout mice exhibited neurological impairments and deficits in SNARE-complex assembly, revealing an important physiological function for α-synuclein of relevance to neurodegene...
10.1002/ajpa.20546
84,442,374
Abstract Capuchins living in Boa Vista (Piauì, Brazil) crack open hard palm nuts on hard, level surfaces (anvils) using stones (hammers) as percussive tools. This activity leaves diagnostic physical remains: distinctive shallow depressions (pits) on the surface of the anvil, cracked shells, and stone hammers on the anv...
10.1038/nature08188
This paper records physical characteristics of capuchin stone tools, providing the first systematic baseline data for comparison with the better-known chimpanzee and archaeological hominin records.
10.1073/pnas.0607909104
38,412,198
Archaeological research in the African rainforest reveals unexpected results in the search for the origins of hominoid technology. The ancient Panin sites from Côte d'Ivoire constitute the only evidence of prehistoric ape behavior known to date anywhere in the world. Recent archaeological work has yielded behaviorally ...
10.1038/nature08188
This paper reports the oldest dated chimpanzee activity area, and establishes a series of test criteria for distinguishing human from non-human artefacts that includes the presence of flaking features and distinct use residues.
10.1126/science.287.5453.664
38,444,163
Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1 α −/− fibroblasts were impaired in JNK activation by ER stress. T...
10.1038/nature07203
This paper shows how ER stress activates JNK by way of IRE1α.
10.1126/science.1128294
41,766,042
Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER...
10.1038/nature07203
This paper shows that decreasing ER stress improves insulin sensitivity in mice with type 2 diabetes.
10.1073/pnas.1215498110
102,168,265
Many drugs and drug candidates are suboptimal because of short duration of action. For example, peptides and proteins often have serum half-lives of only minutes to hours. One solution to this problem involves conjugation to circulating carriers, such as PEG, that retard kidney filtration and hence increase plasma half...
10.1038/natrevmats.2016.71
This study features cleavable covalent linkages with tunable half-lives over a wide range and demonstrates different drug release kinetics by orchestrating the rates of bulk erosion and linkage cleavage independently.
10.1126/science.1247663
41,502,617
Toward Successful Tissue Repair The therapeutic use of growth factors in tissue regeneration has suffered from safety and efficacy issues. Reasoning that the unmet potential may be because of nonphysiological delivery, Martino et al. (p. 885 ) engineered growth factors to bind strongly to extracellular matrix proteins....
10.1038/natrevmats.2016.71
Growth factors were engineered to bind strongly to the extracellular matrix, which led to superior tissue repair and decreased side effects in the treatment of diabetic wounds, compared with the wild-type proteins, which have low affinity to the extracellular matrix.
10.1073/pnas.1413027111
42,611,811
Significance Drug delivery depots used in the clinic today are single use, with no ability to refill once exhausted of drug. Our system exploits nucleic acid complementarity to refill drug-delivering depots through the blood. The utility of this approach is demonstrated by its ability to inhibit tumor growth to a great...
10.1038/natrevmats.2016.71
A new paradigm of refilling hydrogel drug depots that are already present in the body was presented, and the utility of highly specific drug–polymer interactions for this application was also demonstrated.
10.1146/annurev-arplant-042110-103811
122,989,991
Energy conversion of sunlight by photosynthetic organisms has changed Earth and life on it. Photosynthesis arose early in Earth's history, and the earliest forms of photosynthetic life were almost certainly anoxygenic (non-oxygen evolving). The invention of oxygenic photosynthesis and the subsequent rise of atmospheric...
10.1038/nchembio.1555
A comprehensive overview of the evolution of photosynthesis from molecules to organisms
10.1038/ismej.2007.59
19,083,630
Abstract The photosynthetic pigments of phototrophic microorganisms cover different regions of the solar light spectrum. Utilization of the light spectrum can be interpreted in terms of classical niche theory, as the light spectrum offers opportunities for niche differentiation and allows coexistence of species absorbi...
10.1038/nchembio.1555
The authors use model calculations to demonstrate that light absorption by water defines a series of distinct spectral niches in the underwater light spectrum that match the light absorption spectra of the major photosynthetic pigments on Earth
10.1126/science.1191127
20,654,314
Chlorophylls are essential for light-harvesting and energy transduction in photosynthesis. Four chemically distinct varieties have been known for the past 60 years. Here we report isolation of a fifth, which we designate chlorophyll f. Its in vitro absorption (706 nanometers) and fluorescence (722 nanometers) maxima ar...
10.1038/nchembio.1555
An unexpected discovery of a cyanobacterium with a substantial amount of a chlorophyll (Chl f ) that absorbs at far longer wavelengths than the primary electron donors in oxygenic photosynthesis
10.1073/pnas.1002873107
100,318,242
Light is the source of energy for photosynthetic organisms; when in excess, however, it also drives the formation of reactive oxygen species and, consequently, photoinhibition. Plants and algae have evolved mechanisms to regulate light harvesting efficiency in response to variable light intensity so as to avoid oxidati...
10.1038/nchembio.1555
The authors show that in the moss Physcomitrella patens both PsbS and LhcSR are present and actively contribute to nonphotochemical quenching
10.1098/rsif.2013.0901
83,147,076
Photosynthesis begins with light harvesting, where specialized pigment–protein complexes transform sunlight into electronic excitations delivered to reaction centres to initiate charge separation. There is evidence that quantum coherence between electronic excited states plays a role in energy transfer. In this review,...
10.1038/nchembio.1555
This review on the physical aspects of light harvesting explains important concepts such as excitons, (in)coherence and different types of excitation energy transfer. Some basic knowledge of quantum mechanics is required
10.1073/pnas.0502848102
83,442,468
We report free-standing atomic crystals that are strictly 2D and can be viewed as individual atomic planes pulled out of bulk crystals or as unrolled single-wall nanotubes. By using micromechanical cleavage, we have prepared and studied a variety of 2D crystals including single layers of boron nitride, graphite, severa...
10.1038/nature12385
This was the first paper to demonstrate the electric field effect and study electron transport in 2D crystals other than graphene.
10.1126/science.1164680
125,286,940
It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in hum...
10.1038/nature10147
In this study, the authors took advantage of the global pulse of 14 C during the cold war and estimated a rate of cardiomyocyte renewal in human hearts of up to 1% per year.
10.1073/pnas.0706760104
81,040,137
The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of t...
10.1038/nature10147
This study describes the isolation of c-KIT + CPCs from human hearts, and reports their differentiation into cardiomyocytes and vascular elements both in vitro and after transplantation.
10.1073/pnas.0706625104
62,606,619
The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD...
10.1038/nature18850
This study linked the microbiota to IBD and also demonstrated that various forms of the condition have distinct signatures of microbiota.
10.1101/gr.126573.111
62,638,778
The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characteriz...
10.1038/nature18850
This study identified high levels of Fusobacterium nucleatum in tissue from human tumours; the bacterium was later confirmed to cause tumours in experiments in animals.
10.1126/science.1235872
125,323,106
Digoxin Dangers A proportion of patients treated with digoxin, a cardiac glycoside used to treat heart function abnormalities, generate the inactive metabolite, dihydrodigoxin, resulting in poor efficacy. Haiser et al. (p. 295 ) examined a potential culprit responsible for this transformation—the actinobacterium, Egger...
10.1038/nature18850
This study provided a mechanism to underpin the high variation between individuals in efficacy of the cardiac drug digoxin, which was suspected (but not yet proven) to be linked to its metabolism by Eggerthella lenta
10.1126/science.1241214
83,536,166
The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of t...
10.1038/nature18850
This study demonstrated that phenotypes such as increased adiposity could be transferred from people to mice using personalized culture collections.
10.1126/science.1191175
41,714,003
Blocking Interfering Microbes Irinotecan is a widely used anticancer pro-drug that is converted in the liver into the active form, but when it gets into the gut, the normally benign microbial flora can convert it into the toxic form, which kills the rapidly multiplying gut epithelium as it would kill rapidly dividing t...
10.1038/nature18850
This paper demonstrated that the cancer therapeutic drug irinotecan causes severe diarrhoea because of its reactivation and metabolism by bacterial β-glucuronidases; inhibiting these enzymes with a drug that targets the bacteria, rather than the host, reduces toxicity.
10.1073/pnas.0904489106
41,758,151
We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary...
10.1038/nature18850
This study provided the first link between the toxicity of a drug (in this case, acetaminophen, a widely used analgesic) and microbial metabolism.
10.1126/science.1124234
125,332,538
The human intestinal microbiota is composed of 10 13 to 10 14 microorganisms whose collective genome (“microbiome”) contains at least 100 times as many genes as our own genome. We analyzed ∼78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction–amplified 16 S ribosomal DNA sequences obtained fr...
10.1038/nature18850
This study provided the first metagenomic gene catalogue of the human gut.
10.1126/science.1159850
17,716,619
Nonribosomal peptide synthetases (NRPSs) are modular multidomain enzymes that act as an assembly line to catalyze the biosynthesis of complex natural products. The crystal structure of the 144-kilodalton Bacillus subtilis termination module SrfA-C was solved at 2.6 angstrom resolution. The adenylation and condensation ...
10.1038/nchembio.1883
This paper describes the first X-ray structure of an intact NRPS termination module.
10.1257/aer.102.1.131
83,341,457
This paper introduces endogenous and directed technical change in a growth model with environmental constraints. The final good is produced from “dirty” and “clean” inputs. We show that: (i) when inputs are sufficiently substitutable, sustainable growth can be achieved with temporary taxes/subsidies that redirect innov...
10.1038/nclimate3113
Presents a general model clarifying conditions under which green growth is possible or impossible.
10.1111/j.1749-6632.2010.05921.x
100,339,784
This paper reviews the mainstream, resource economics, and ecological economics models of growth. A possible synthesis of energy‐based and mainstream models is presented. This shows that when energy is scarce it imposes a strong constraint on the growth of the economy; however, when energy is abundant, its effect on ec...
10.1038/nclimate3113
Provides an overview of both orthodox and heterodox studies of the importance of energy quantity and quality for economic growth.
10.1111/mmi.12745
100,716,452
Summary The relative localization patterns of class B penicillin‐binding proteins Pbp2x and Pbp2b were used as positional indicators of septal and peripheral (side‐wall‐like) peptidoglycan ( PG ) synthesis, respectively, in the mid‐cell regions of S treptococcus pneumoniae cells at different stages of division. We conf...
10.1038/nchembio.2109
Beautiful combination of FDAAs, Van-FL, β-lactams and fusion proteins to explore PBP localization during division.